HIV-associated neurocognitive disorders (HAND) are common in the era of combined antiretroviral therapy (ART) and are a significant burden on public health resources. Yet current standard-of-practice methods for screening and ascertaining the everyday functioning impact of HAND are generally insensitive, outdated, and/or highly impractical for routine use in clinic, which may adversely affect health outcomes by leaving many individuals with syndromic HAND undiagnosed and untreated. Advances in Internet technology may provide an especially germane, naturalistic, user-friendly, and contemporary platform upon which to develop the next generation of everyday functioning assessments for HAND. Of note, the everyday functioning independence of individuals living with HIV infection is increasingly dependent on navigation of the World Wide Web to engage medical (e.g., pharmacy and health information), household (e.g., shopping and banking), and even psychosocial (e.g., social networking) resources. As such, the ecological validity and viability of the next generation of everyday functioning outcomes in neuroAIDS necessitates the development of Internet-specific performance- based tasks in order to enhance diagnosis and treatment of HAND. The aim of this R21 is to validate a series of novel, innovative tasks of everyday functioning (i.e., household shopping, financial management) that use a realistic, state-of-the-art web-based approach to evaluating HAND. The portability and health-relevance of these assessments are enhanced by a developmental aim that will engineer and pilot a naturalistic online health literacy search measure and a pharmacy refill and communication task on a mobile platform. We propose to recruit 100 persons with HIV infection (with a 50% prevalence of HAND) and 50 seronegative subjects from ongoing studies within the UCSD HIV Neurobehavioral Research Program (HNRP), thereby leveraging the comprehensive clinical characterization of these subjects at no cost to this grant. It is hypothesized that HIV infection will be associated with worse real world functioning on these web-based tasks, which will correlate with well-validated measures of health literacy (e.g., knowledge), neurocognition (e.g., executive dysfunction), and everyday functioning (e.g., medication management). It is expected that the web-based assessments will improve the diagnostic classification of HAND as compared to current standard- of-practice approaches. Accordingly, this R21 application proposes an important first step in determining whether Internet technology can be used to more accurately and effectively determine the real world impact of HIV infection.